The effector molecules of the immune system include a repertoire of circulating immunoglobulins non-attributable to exogenous antigenic induction, variously referred to as xe2x80x9cautoantibodiesxe2x80x9d or xe2x80x9cnatural antibodiesxe2x80x9d. The existence of such antibodies has been long recognized and their various proposed functions may be classed as xe2x80x9cself-attackxe2x80x9d or xe2x80x9cself-benefitxe2x80x9d. For the former, the specter of autoimmunity is raised and the term xe2x80x9cautoantibodiesxe2x80x9d is customarily applied. For the latter, the term xe2x80x9cautoantibodiesxe2x80x9d is customarily applied. For the latter, designated xe2x80x9cnatural; antibodiesxe2x80x9d, support of homeostasis is implied.
U.S. patent application Ser. No. 08/271,210 filed Jul. 5, 1994, discloses a circulating natural human antibody immunoreactive with an arginine-rich epitope present on human protamine. U.S. Pat. No. 5,606,026 issued Feb. 25, 1997, discloses that the arginine-rich epitope is present in the Tat protein of HIV-1 and further discloses a second circulating human natural antibody immnunoreactive with a different epitope on the Tat protein of HIV-1. In addition, a third circulating human natural antibody immunoreactive with a cryptic epitope present on human lactoferrin is disclosed therein.
It has been shown that all three of the above-mentioned circulating human natural antibodies decrease after HIV infection reaching minimal levels as the patient progresses to AIDS. These antibodies are found in all sera of normal humans of all ages, from cord blood to adult, which, by virtue of their ubiquitous occurrence, are identified as natural antibodies.
Therefore, what is needed in the art are the monoclonal counterparts of these circulating human natural antibodies for their therapeutic and diagnostic uses.
The present invention provides monoclonal forms of human natural antibodies.
In one aspect, the present invention provides hybridoma cell line RWL-1 (ATCC CRL 12431), a product of the fusion of Epstein Barr virus (EBV) transformed umbilical cord blood cells and HMMA, mouse: human heteromyeloma cells.
In another aspect, the present invention provides monoclonal human IgM antibodies, produced by RWL-1 cells.
In yet another aspect, the present invention provides another hybridoma cell line, RWT-4 (ATCC CRL 12472), a product of the fusion of EBV-transformed umbilical cord cells with SHM-D33 cells (ATCC CRL 1668), mouse: human heteromyeloma cells.
In yet another aspect, the present invention provides monoclonal human IgM antibodies produced by RWT-4 cells.
In a still further aspect, the present invention provides hybridoma cell line RWT-12 (ATCC CRL 12477), a product of the fusion of EBV-transformed human umbilical cord cells and HMMA, mouse: human heteromyleoma cells.
In a still further aspect, the present invention provides monoclonal human IgM antibodies produced by RWT-4 cells.
In a still further aspect, the present invention provides a method for treating a patient suffering from an infection caused by HIV-1 comprising administering to a patient in need of such treatment an effective amount for treating said infection of a monoclonal antibody selected from the group consisting of antibodies produced by RWT-4 cells, RWT-12 cells, and mixtures thereof.
In a still further aspect, the present invention provides a method for increasing CD4+T cells in a patient suffering from an infection caused by HIV-1 comprising administering an amount for increasing CD4+T cells of antibodies produced by hybridoma cells having Accession Nos. ATCC CRL 12472 , ATCC CRL 12477 and mixtures thereof.
In a still further embodiment, the present invention provides a pharmaceutical formulation comprising isolated human IgM monoclonal antibodies selected from the group consisting of antibodies produced by hybridoma cell lines having Accession Nos. ATCC CRL 12472, ATCC CRL 12477, mixtures thereof and a pharmaceutical acceptable vehicle.